Impaired fibrinolytic activity in type II diabetes: correlation with urinary albumin excretion and progression of renal disease.

Progression of renal disease and cardiovascular complications in type II diabetes mellitus have been shown to correlate with control of blood glucose, lipids, blood pressure, and smoking. These factors, however, do not appear to totally explain these diabetic complications. Renal disease and cardiovascular complications in type II diabetes are associated with vascular abnormalities and fibrosis, both of which may occur with impaired fibrinolysis. A cross-sectional study was therefore performed in 107 type II diabetic patients recruited from the Denver Metropolitan Area to examine the effect of impaired fibrinolysis, as assessed by the ratio of plasminogen activator inhibitor (PAI-1) to tissue-type plasminogen activator (t-PA). With urinary albumin excretion (UAE) as a risk factor for both renal disease progression and cardiovascular complications, the patients were analyzed with respect to UAE less than and greater than 1 gm/day. The age, blood glucose, hemoglobin A1C, duration of diabetes, lipids, body mass index, and smoking were no different between the groups. As expected, the group with greater UAE had worse renal function, the serum creatinine (1.98 +/- 0.24 vs 1.21 +/- 0.05 mg/dl, P < 0.001) and creatinine clearance (55.5 +/- 6.0 vs 76.8 +/- 2.7 ml/min, P < 0.001) were significantly different. The type II diabetic patients with greater UAE exhibited significantly higher PAI-1/t-PA (2.43 +/- 0.26 vs 1.85 +/- 0.07, P < 0.03). The past history of cardiac complications was also higher (87.5 vs 72.3%, P < 0.07) in the diabetic patients with more impaired fibrinolysis and greater UAE. Thus a prospective, randomized clinical trial in type II diabetes with PAI-1 inhibitors is needed.

Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes.

OBJECTIVE: The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications. The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy, retinopathy, and neuropathy. RESEARCH DESIGN AND METHODS: The 470 hypertensive subjects, defined as having a baseline diastolic blood pressure of > or = 90 mmHg, were randomized to intensive blood pressure control (diastolic blood pressure goal of 75 mmHg) versus moderate blood pressure control (diastolic blood pressure goal of 80-89 mmHg). RESULTS: The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group. During the 5-year follow-up period, no difference was observed between intensive versus moderate blood pressure control and those randomized to nisoldipine versus enalapril with regard to the change in creatinine clearance. After the first year of antihypertensive treatment, creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria. In contrast, patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5-6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy. There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria (25% intensive therapy vs. 18% moderate therapy, P = 0.20) or microalbuminuria to overt albuminuria (16% intensive therapy vs. 23% moderate therapy, P = 0.28). Intensive therapy demonstrated a lower overall incidence of deaths, 5.5 vs. 10.7%, P = 0.037. Over a 5-year follow-up period, there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy. In addition, the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy. CONCLUSIONS: Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period. The more intensive blood pressure control decreased all-cause mortality.

Deletion polymorphism of the angiotensin converting enzyme gene is associated with an increase in left ventricular mass in men with type 2 diabetes mellitus.

Previous studies evaluating the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism have revealed that expression of the DD genotype is associated with an increase in myocardial infarction, cardiomyopathy, and left ventricular (LV) mass in nondiabetic patients. In the present study, a cross-sectional analysis was performed to evaluate the potential relationship between the ACE I/D genotypes and the LV mass index in 289 non-insulin-dependent diabetes mellitus (NIDDM) subjects without known coronary artery disease. Two dimensional directed M-mode echocardiograms along with selected patient characteristics were obtained from the study population. The distribution of the I/D polymorphism was as follows: 63 were II (22%), 137 were ID (47%), and 89 were DD (31%). Univariately, the DD genotype was associated with an increase in LV mass in men but not in women. When subjected to a multiple regression model that included age, systolic blood pressure, duration of diabetes, duration of hypertension, presence of the black race, and the presence of the DD genotype, the DD genotype was independently associated with an increase in the LV mass index with a parameter estimate of 10.5 g/m2 (95% CI = 3.9, 17.0; P < .002) in the male subjects. Thus, in this NIDDM study population, male patients with the DD genotype are independently associated with an increased LV mass.

Antihypertensive therapy in type 2 diabetes: implications of the appropriate blood pressure control in diabetes (ABCD) trial.

As the population ages, the incidence of type 2 diabetes will increase as will the incidence of concomitant vascular complications. Hypertension substantially increases the risk of cardiovascular disease in patients with diabetes. Results from the recent Appropriate Blood Pressure Control in Diabetes (ABCD) trial demonstrated an advantage of an angiotensin-converting enzyme (ACE) inhibitor (enalapril) over a long-acting calcium antagonist (nisoldipine) with regard to the incidence of cardiovascular events over a 5-year follow-up period in hypertensive persons with type 2 diabetes. This trial was a prospective, randomized, blinded study comparing the effects of moderate blood pressure control (target diastolic pressure 80-89 mm Hg) with those of intensive control (target diastolic pressure 75 mm Hg) on the incidence and progression of diabetic vascular complications. The study also compared nisoldipine with enalapril as first-line antihypertensive therapy in terms of prevention and progression of complications of diabetes. In 470 hypertensive patients, the incidence of fatal and nonfatal myocardial infarctions was significantly (p = 0.001) higher among those receiving nisoldipine (n = 25) compared with those receiving enalapril (n = 5). Comparison with previous studies suggests that the difference observed between nisoldipine and enalapril resulted from a beneficial effect of enalapril rather than a deleterious effect from nisoldipine. Since these findings in the ABCD trial are based on a secondary endpoint, they require confirmation. Nevertheless, they suggest that ACE inhibitors should be the initial antihypertensive medication used in patients with type 2 diabetes and hypertension.

Overt albuminuria predicts diabetic retinopathy in Hispanics with NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) occurs with a higher frequency in Hispanic as compared with non-Hispanic whites. It also appears that there is a higher prevalence of diabetic nephropathy in the Hispanic population when compared with non-Hispanic whites. In the current study, 144 Hispanics and 671 non-Hispanic white NIDDM subjects were studied to determine the possible association of various risk factors and diabetic complications, including overt albuminuria, with diabetic retinopathy. Stereoscopic retinal fundus photographs were obtained and graded by the University of Wisconsin Fundus Photographic Reading Center. We also sought to determine whether risk factors for retinopathy vary between Hispanics and non-Hispanic whites. In the total group, duration of diabetes, glycosylated hemoglobin, neuropathy, diastolic hypertension, use of insulin, and Hispanic ethnicity correlated with the presence of retinopathy. Controlling for severity and duration of diabetes, Hispanics had a significantly increased risk of retinopathy relative to non-Hispanic whites (OR = 2.13, 95% CI = 1.34, 3.37, P = 0.0013). Duration of diabetes and presence of neuropathy were significantly correlated with the presence of diabetic retinopathy in Hispanics and non-Hispanic whites. The presence of overt albuminuria (>200 microg/min), although not related to diabetic retinopathy in non-Hispanic whites, conferred a high risk for diabetic retinopathy in Hispanics (OR = 11.14, CI = 1.20, 103.39, P = 0.0339) independent of other risk factors. In summary, Hispanics with NIDDM have an increased prevalence of diabetic retinopathy when compared with non-Hispanic whites. In addition, overt albuminuria in the Hispanic subjects appears to be a powerful predictor of the diabetic retinopathy.

The association between diabetic complications and exercise capacity in NIDDM patients.

OBJECTIVE: Exercise capacity has been used as a noninvasive parameter for predicting cardiovascular events. It has been demonstrated previously in NIDDM patients that several risk factors (i.e., obesity, smoking, hypertension, and African-American race) are associated with an impaired exercise capacity. We studied 265 male and 154 female NIDDM patients who underwent graded exercise testing with expired gas analyses to determine the possible influences of diabetic neuropathy, nephropathy, and retinopathy on exercise capacity. RESEARCH DESIGN AND METHODS: Univariate and multiple linear regression analyses were performed to determine the relationship between diabetic neuropathy, urinary albumin excretion (UAE), and retinopathy with respect to peak oxygen consumption (VO2). Neuropathy was assessed by neurological symptom and disability scores, autonomic function testing, and quantitative sensory exams involving thermal and vibratory sensation. Three categories of UAE were used: normal albuminuria (< 20 micrograms/min), microalbuminuria (20-200 micrograms/min), and overt albuminuria (> 200 micrograms/min). Retinopathy was assessed by stereoscopic fundus photographs. Multiple linear regression analyses were then performed controlling for age, sex, length of diagnosed diabetes, duration of hypertension, race and ethnicity, GHb, BMI, and smoking to determine whether there was an independent effect of these diabetic complications on exercise capacity. RESULTS: Univariate analyses revealed that the presence of diabetic retinopathy (P = 0.03), neuropathy (P = 0.002), microalbuminuria (P = 0.04), and overt albuminuria (P = 0.06) were associated with a lower peak VO2. Multiple linear regression analyses were performed to determine independent relationships with peak VO2. The results revealed that increasing retinopathy stage (Parameter estimate [PE] = -0.59 +/- 0.3 ml.kg-1.min-1; P = 0.026) and increasing UAE stage (PE = -0.62 +/- 0.3 ml.kg-1.min-1; P = 0.04) were associated with a decrease in peak VO2. CONCLUSIONS: In the present study of NIDDM subjects, a significant independent association was demonstrated between diabetic nephropathy and retinopathy with exercise capacity. These results were obtained controlling for age, sex, length of diagnosed diabetes, hypertension, race, and BMI. Thus the findings in this large NIDDM population without a history of coronary artery disease indicate a potential pathogenic relationship between microvascular disease and exercise capacity.

The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension.

BACKGROUND: It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications. Because this issue remains controversial, we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were randomly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study. METHODS: The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective, randomized, blinded trial comparing the effects of moderate control of blood pressure (target diastolic pressure, 80 to 89 mm Hg) with those of intensive control of blood pressure (diastolic pressure, 75 mm Hg) on the incidence and progression of complications of diabetes. The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes. In the current study, we analyzed data on a secondary end point (the incidence of myocardial infarction) in the subgroup of patients in the ABCD Trial who had hypertension. RESULTS: Analysis of the 470 patients in the trial who had hypertension (base-line diastolic blood pressure, > or = 90 mm Hg) showed similar control of blood pressure, blood glucose and lipid concentrations, and smoking behavior in the nisoldipine group (237 patients) and the enalapril group (233 patients) throughout five years of follow-up. Using a multiple logistic-regression model with adjustment for cardiac risk factors, we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infarctions (a total of 24) than enalapril (total, 4) (risk ratio, 9.5; 95 percent confidence interval, 2.7 to 33.8). CONCLUSIONS: In this population of patients with diabetes and hypertension, we found a significantly higher incidence of fatal and nonfatal myocardial infarction among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril. Since our findings are based on a secondary end point, they will require confirmation.

Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy.

Previous studies have shown that the angiotensin-converting enzyme (ACE) gene polymorphism is associated with an increased risk of vascular disease in non-diabetic patients. The present study was conducted on 509 NIDDM patients who underwent a screening test to determine their ACE genotype for the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Various baseline indices were correlated with the three ACE polymorphisms. The genotype was determined through polymerase chain reaction amplification of the angiotensin-converting enzyme polymorphism. The univariate relationship between the presence of the DD genotype with nephropathy as measured by urinary albumin excretion (UAE), and a history coronary artery disease (CAD) was then examined. Finally, a multiple model for each UAE and CAD was created so as to determine the independent effects of the presence of the DD genotype on each diabetic complication. Univariately, the presence of the DD genotype was associated with diabetic nephropathy. Furthermore, in a multiple model predicting diabetic nephropathy, the presence of the DD genotype was independently associated with diabetic nephropathy (odds ratio = 2.8, 95% confidence interval 1.4 to 5.5) but not CAD. Thus, the ACE DD genotype in 509 non-Hispanic white NIDDM patients in a metropolitan area in the U.S. was independently associated with the presence of diabetic nephropathy and, therefore, may be potentially used as a marker for NIDDM patients at risk for developing diabetic nephropathy.

Increased complications in noninsulin-dependent diabetic patients treated with insulin versus oral hypoglycemic agents: a population study.

A cross-sectional population study was performed in a cohort of 890 non-insulin-dependent diabetes mellitus (NIDDM) patients residing in the greater Denver metropolitan region. Its purpose was to evaluate the relationship between insulin and oral hypoglycemic agents (OHAs) with regard to metabolic control and diabetic complications. The mean glycosylated hemoglobin for patients treated with insulin was 12.0 +/- 0.15% versus 11.4 +/- 0.14% (p < .03) for OHA. The difference in fasting blood sugar for the insulin-treated group (195.0 +/- 3.5 mg/dl) versus the OHA-treated group (194.0 +/- 2.9 mg/dl) was not statistically significant. Categorical increases in urinary albumin excretion were associated positively within insulin versus OHA therapy (p < .0001). Patients treated with insulin therapy had a higher frequency of peripheral vascular disease (insulin therapy, 14%; OHA therapy, 10%; p < .05); neuropathy (insulin therapy, 55%; OHA therapy, 37%; p < .0001); and retinopathy (insulin therapy, 71%; OHA therapy, 45%; p < .0001). The frequency of cardiovascular disease was equivalent in the two groups (17% versus 13%). In protocols correcting for diabetes duration, glycosylated hemoglobin, and gender in a multivariate model, the use of insulin still was related significantly to increases in urinary albumin excretion (p < .01), retinopathy (p < .0001), and neuropathy (p < .0008). In a subgroup of individuals with diabetes duration > 10 years (n = 211 for insulin treatment, n = 118 for OHA treatment), the frequency of neuropathy still was significantly higher in the insulin group (63% vs 49%; p < .016) as was retinopathy (85% vs 58%; p < .0001). Overt albuminuria also was more significant in the insulin-treated patients (p < .04). In summary, the NIDDM patients treated with insulin had more nephropathy, retinopathy, and neuropathy than did NIDDM patients treated with OHA, independent of duration of diabetes, fasting blood glucose, glycosylated hemoglobin, age, and blood pressure level. These results in NIDDM patients may be due to contributions from worse blood glucose control at an earlier stage in the patients' diabetes and/or the mitogenic, atherogenic, thrombogenic, and vascular permeability effects of insulin.

Appropriate Blood Pressure Control in NIDDM (ABCD) Trial.

The ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is a large, prospective, randomized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus (NIDDM) designed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in NIDDM. The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and an angiotensin-converting-enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations aged 40-74 years, 470 hypertensive patients (diastolic blood pressure of > or = 90.0 mmHg at time of randomization) and 480 normotensive patients (diastolic blood pressure of 80.0 mmHg at time of randomization). The study duration is 5 years and is scheduled to end in May of 1998. Patients are randomized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients are also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control is necessary. The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance. Secondary outcome measures are urinary albumin excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. Given the data showing the impact of hypertension on complications in NIDDM, the ABCD Trial is designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM.

Urinary albumin excretion as a predictor of diabetic retinopathy, neuropathy, and cardiovascular disease in NIDDM.

OBJECTIVE: The relationship between urinary albumin excretion (UAE) and diabetic complications in NIDDM has not been studied in a large American population. The demonstrated relationship between increased UAE and the development of retinopathy, nephropathy, and neuropathy in IDDM makes this an important issue to also be studied in NIDDM patients. RESEARCH DESIGN AND METHODS: A large population study of 947 NIDDM patients living predominantly in a metropolitan area was undertaken. Three categories of UAE, namely, normal albuminuria (< 20 micrograms/min), microalbuminuria (20-200 micrograms/min), and overt albuminuria (> 200 micrograms/min) were compared with 1) retinopathy as assessed by stereoscopic fundus photographs; 2) cardiovascular disease as assessed by a history of cardiac disease or stroke; ischemic changes on exercise treadmill testing; Q wave myocardial infarction; Estes, Sokolow, or Cornell criteria for left ventricular hypertrophy; positive Rose questionnaire for angina; and an abnormal Doppler exam for peripheral vascular disease; and 3) neuropathy as assessed by neurological symptom and disability scores, autonomic function testing, and quantitative sensory exams involving thermal and vibratory sensation. Selected patient characteristics were then evaluated to determine their effects on the presence of diabetic complications using univariate analyses. Multiple logistic regression analyses were then performed to determine the independent effect of UAE on these diabetic complications. RESULTS: chi 2 analyses revealed that UAE was significantly associated with the presence of retinopathy (P < 0.001), neuropathy (P < 0.001), and cardiovascular disease (P < 0.001). In the multiple logistic regression analyses, UAE had strong independent associations with retinopathy, neuropathy, and cardiovascular disease. CONCLUSIONS: Thus, increasing UAE in this large NIDDM population in the U.S. was associated with an increased prevalence of diabetic retinopathy, neuropathy, and cardiovascular disease. This suggests that UAE may be more than an indicator of renal disease in NIDDM patients and, in fact, may reflect a state of generalized vascular damage occurring throughout the body. Prospective studies in NIDDM patients are needed to determine the predictive effect of UAE and the effect of decreasing UAE on future diabetic micro- and macrovascular complications.

Baseline characteristics of participants in the Appropriate Blood Pressure Control in Diabetes trial.

The ABCD (Appropriate Blood Pressure Control in Diabetes) trial is a large, prospective, randomized clinical trial designed to compare the effects of intensive with moderate blood pressure control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in non-insulin-dependent diabetes (NIDDM). The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and of an angiotensin-converting enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations: a hypertensive one (diastolic blood pressure of > or = 90.0 mm Hg at the time of randomization) and a normotensive one (diastolic blood pressure of 80.0-89.0 mm Hg at the time of randomization). A total of 950 men and women aged 40-74 years were randomized and are being followed for 5 years at a single center. There were 470 randomized participants in the hypertensive population and 480 randomized participants in the normotensive population. This report summarizes the demographic, biochemical, and clinical characteristics of the randomized patients at the time of entry into the trial and evaluates the balance between the treatment groups within each population.

Effect of risk factors on exercise capacity in NIDDM.

Exercise capacity has been used as a noninvasive parameter for predicting cardiovascular events. It is known that diabetic patients have an impaired exercise capacity when compared with nondiabetic age-matched control subjects, but the risk factors associated with this impairment have not been thoroughly analyzed. A total of 453 male and female NIDDM patients who underwent graded exercise testing with expired gas analysis were studied to determine the possible influences of demographic and cardiac risk factors on exercise capacity. Univariate and multiple linear regression analyses were performed on baseline patient characteristics with respect to peak oxygen consumption (VO2). In the regression analyses, African-American race was strongly associated with a decrease in peak VO2; the difference in means between African-Americans and other subjects for men was -2.50 ml.kg-1.min-1 (-4.28, -0.07, 95% CI) (P < 0.006) and for women was -2.96 ml.kg-1.min-1 (-4.45, -1.47) (P < 0.0002). Univariate analyses revealed that African-American subjects had increased prevalence, longer duration, and higher systolic and diastolic hypertension than the non-Hispanic and Hispanic whites. Other independent predictors of peak VO2 (reported as change in peak VO2 in milliliters per kilogram per minute) were BMI (men: -0.39 kg/m2 [-0.52, -0.29], P < 0.0001; women: -0.39 kg/m2 [-0.48, -0.31], P < 0.0001), age (men: -0.16/year [-0.23, -0.09], P < 0.0001; women: -0.17/year [-0.24, -0.11], P < 0.0001), baseline resting systolic blood pressure (men: -0.03/mmHg [-0.06, -0.01], P < 0.05; women: -0.03/mmHg (-0.06, -0.01)f1p4< 0.05), and pack-years smoking (men: -0.04/pack-years [-0.04, -0.01], P < 0.01; women: -0.04/pack-years [-0.07, -0.01], P < 0.0001). Thus, in this large NIDDM study, weight loss, smoking cessation, and aggressive blood pressure control, particularly in African-Americans with NIDDM, would appear to be important in improving exercise capacity and potentially improving the increased cardiovascular mortality associated with an impaired exercise capacity.

Clinical factors associated with urinary albumin excretion in type II diabetes.

Clinical factors associated with urinary albumin excretion (UAE) in type II diabetes are less well known than in type I diabetes. To examine the factors associated with UAE in type II diabetes, 933 Appropriate Blood Pressure Control in Diabetes Trial patients were classified according to UAE status: normoalbuminuria (< 20 micrograms/min), microalbuminuria (20 to 200 micrograms/min), and macroalbuminuria (> 200 micrograms/min). The class of UAE was then correlated with various clinical factors. Using univariate analyses, Hispanic ethnicity, African-American race, male gender, poor glycemic control, insulin use, long duration of diabetes, dyslipidemia, diastolic and systolic hypertension, smoking, and obesity were significantly correlated with microalbuminuria and macroalbuminuria. Using multivariate logistic regression analyses controlling for diabetes duration, glycosylated hemoglobin, gender, and race, the most significant predictors of microalbuminuria and macroalbuminuria were systolic hypertension, body mass index, high-density lipoprotein cholesterol, insulin use, and smoking pack-years. Of these factors, several are potentially reversible with aggressive intervention.

The ABCD (Appropriate Blood Pressure Control in Diabetes) trial. Rationale and design of a trial of hypertension control (moderate or intensive) in type II diabetes.

OBJECTIVE: The primary objective of the ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is to determine the efficacy of intensive versus moderate antihypertensive control on the outcome of type II diabetic end-organ complications in normotensive and hypertensive populations. The secondary objective is to determine whether any differential effect on end-organ complications exists between an angiotensin converting enzyme inhibitor (enalapril) and a calcium channel blocker (nisoldipine). DESIGN: The ABCD Trial is a prospective, controlled, randomized, double-blind trial, with a planned follow-up of 5 years. SETTING: All patients are seen at the Colorado Prevention Center, site of the ABCD Trial, for follow-up visits. PATIENTS: Patients are type II diabetic males and females between the ages of 40 and 74 years with entry diastolic blood pressures > or = 80 mmHg. Patients were recruited from University of Colorado-affiliated hospitals, several health maintenance organizations, and mailing lists from the Colorado affiliate of the American Diabetes Association. INTERVENTIONS: Patients were randomized to intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients were also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control was necessary. MAIN OUTCOME MEASURES: The primary outcome measure is glomerular filtration rate as assessed by 24-hour creatinine clearance. Secondary outcome measures are microalbumin urinary excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. CONCLUSION: Given the data showing the impact of hypertension on diabetic complications, the ABCD Trial was designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of these complications. Results from the ABCD Trial are expected to lend interpretable and clinically relevant findings with regards to the treatment of hypertension in type II diabetes.